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F Tassone

Publications and source records attributed to F Tassone.

At least 73 records · Page 4Linked to original sources
PubMed1997

Map location, genomic organization and expression patterns of the human RED1 RNA editase.

A cDNA fragment containing sequences homologous to the rat RED1 RNA editase gene was recently identified on human chromosome 21. Here we report the location of this cDNA in distal 21q22.3 near the CD18 gene. We also report isolation of cDNA clones containing the complete coding region of the human RED1 gene, and use of this sequence to determine the genomic structure from overlapping cosmids. Human RED1 spans approximately 25 kb and is composed of 10 exons containing coding sequences. The two RNA binding domains are located within a single large, 935 nucleotide, exon 2. An alternatively processed exon 6 potentially interrupts the catalytic domain. Exon 10 is largely composed of the 3' untranslated region, which is unusually high in GC content and contains a segment that is > 90% identical with the 3' UT of the homologous rat gene. A survey of expression patterns reveals differential processing of the 5 and 8.5 kb transcripts in all sources examined. The difference in transcript size likely results from alternative processing in the 3' UT. Potential relevance of overexpression of RED1 to the development of the Down Syndrome phenotype is discussed.

Adenosine Deaminase↗
PubMed1997

In obesity, glucose load loses its early inhibitory, but maintains its late stimulatory, effect on somatotrope secretion.

Glucose load has a biphasic effect on GH secretion. In fact, in normal subjects, glucose load has a prompt inhibitory and a late stimulatory effect on both spontaneous and GHRH-induced GH levels. The mechanism underlying the inhibitory effect is probably mediated by the increase in hypothalamic somatostatin, whereas that underlying the stimulatory effect is unclear. On the other hand, in obesity, a reduced somatotrope responsiveness to all GH secretagogues is well known, whereas recently, we found that glucose load, but not pirenzepine and somatostatin, fails to inhibit the GHRH-induced GH rise. Thus, the inhibitory effect of hyperglycemia on GH secretion is selectively lacking in obesity. The aim of the present study was to verify whether in obesity the late stimulatory effect of glucose on GH secretion is preserved. We studied 15 female obese patients (OB; age, 33.9 +/- 2.6 yr; body mass index, 36.4 +/- 1.5 kg/m2; waist/hip ratio, 0.9 +/- 0.1) and 12 normal female subjects (NS; 26.5 +/- 1.0 yr; 21.4 +/- 0.3 kg/m2) as controls. Two studies were performed. In study A (six OB and six NS) we evaluated the somatotrope response to GHRH (1 microgram/kg, i.v., at 0 min) alone or preceded by oral glucose (OGTT; 100 g, orally, at -45 min). In study B (nine OB and six NS) we studied the somatotrope response to OGTT (100 g, orally, at 0 min), saline plus GHRH (1 microgram/kg, iv, at 150 min), and OGTT plus GHRH. In study A, the GHRH-induced GH rise in NS was higher (P < 0.01) than that in OB. OGTT blunted the GHRH-induced GH rise in NS (0-90 min area under the curve, 318.9 +/- 39.1 vs. 696.3 +/- 110.8 micrograms/min-L; P < 0.05), but failed to modify it in OB (289.1 +/- 51.7 vs. 283.9 +/- 44.0 micrograms/min-L). In study B, the GHRH-induced GH rise in NS was higher (P < 0.01) than that in OB. OGTT induced a late GH increase in both NS (150-240 min area under the curve, 249.6 +/- 45.2 micrograms/min-L) and OB (103.2 +/- 31.4 micrograms/min-L). Moreover, OGTT enhanced the GHRH-induced GH rise in NS as well as in OB [1433.0 +/- 202.0 vs. 967.9 +/- 116.3 micrograms/min-L (P < 0.03) and 763.8 +/- 131.0 vs. 278.1 +/- 52.3 micrograms/min-L (P < 0.01), respectively]. The GH responses to OGTT alone and combined with GHRH in OB were lower (P < 0.03) than those in NS. Our data show that in human obesity, the oral glucose load loses its precocious inhibitory effect on the GHRH-induced GH rise but maintains its late stimulatory effect on somatotrope secretion. These findings suggest that the inhibitory and stimulatory effects of glucose load on GH secretion are unlikely to be due to biphasic modulation of hypothalamic somatostatin release, which seems selectively refractory to stimulation by hyperglycemia in obesity.

Adult↗
PubMed1995

A search for genes from the dark band regions of human chromosome 21.

As part of an effort to isolate genes from the entire long arm of human chromosome 21, we performed cDNA selection with 15 YACs from the regions of the pericentromeric heterochromatin and the two Giemsa dark bands of this chromosome using cDNA libraries from six different tissues. Nine of these YACs mapped to the Giemsa dark band, 21q21. The 9 YACs cover approximately 6 Mb of DNA, representing 15% of 21q and a significant portion of the 12-15 Mb estimated to be within this band. Several lines of evidence from analysis of the selected cDNA libraries suggest that this region of 21q has very few single-copy transcribed sequences. An EcoRI library was constructed with DNA from 1 of the 9 YACs. Grail analysis of the sequences of both ends of 24 YAC-specific clones from this EcoRI library revealed no potential exons. In contrast to these results, the selected cDNA libraries of a control YAC from the human MHC region in 6p21.3 as well as those from most of the other 21q YACs consisted largely of YAC-specific single-copy cDNA clones. Given the success of the cDNA selection method for finding a large number of genes in YACs from other chromosomal regions, these results suggest that the 6 Mb of DNA in the dark band 21q21 contains few single-copy sequences expressed in this tissue set. In contrast, selected cDNA libraries from the pericentromeric region, the telomeric border of the dark band 21q21, and the dark band 21q22.2 yielded more than 30 new ESTs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

cDNA selection from 10 Mb of chromosome 21 DNA: efficiency in transcriptional mapping and reflections of genome organization.

The technique of cDNA hybridization selection has been applied individually to 16 YAC clones mapping to various regions of the long arm of human chromosome 21. YACs represented approximately 10 Mb of non-overlapping DNA, and cDNA sources included fetal brain, whole fetus, and adult testes, thymus, liver and spleen. Sequencing, Northern analysis, RT-PCR and cDNA library screenings have been used to identify and partially characterize a non-redundant set of novel genes. A preliminary analysis strategy of the selected cDNAs has proven rapid and effective for isolation of the more highly represented genes and is suitable for survey transcriptional mapping efforts. By scaling up to screen > 1000 cDNA fragments per 100 kb of YAC DNA, more rare transcripts are identified and lead to comprehensive gene maps. Strong regional variations in transcriptional activity were observed, with gene densities ranging from < 1/2000 kb to > 1/15 kb. This effort has produced a large number of new genes of potential relevance to Down Syndrome.

Adult↗
PubMed1994

Highly polymorphic repeat marker within the beta-amyloid precursor protein gene.

We have identified a polymorphic compound dinucleotide repeat sequence in intron 1 of the beta-amyloid precursor protein (APP) gene on chromosome 21. Using polymerase chain reaction (PCR) amplification of the locus, designated APPivs1, we detected 13 alleles in the CEPH family members (heterozygosity = 0.69). Lod score analysis showed complete linkage of the marker to the loci D21S210 and D21221.

Alleles↗
PubMed1993

Molecular and cytogenetic characterization of a Chinese hamster/human hybrid cell line containing a der (21)t(Ypter-->cenY::cen21-->21qter) chromosome.

Human/rodent somatic cell hybrids have been exceedingly useful in assigning human genes and DNA sequences to specific human chromosomes. As new technologies for analyzing the human chromosome complement of such human/rodent hybrid cells become available, it is of critical importance that these be applied to enhance characterization of existing hybrids. This is particularly important since human chromosomes in such hybrids have been observed to rearrange with time. We report here the use of fluorescence in situ hybridization of DNA probes to metaphase chromosomes to analyze one hybrid designated 72532X6. This analysis shows that the chromosome suspected to be a normal human chromosome 21 in this hybrid is actually a translocation chromosome containing Yp and 21q. In addition, the hybrid contains a fragment of human chromosome 9 translocated to a Chinese hamster chromosome. Analysis of the chromosomes from the human donor indicates that his chromosomes are normal. Thus, this translocation chromosome appears to have arisen after formation of the hybrid.

Animals↗
PubMed1992

Analysis of chromosome 21 yeast artificial chromosome (YAC) clones.

Chromosome 21 contains genes relevant to several important diseases. Yeast artificial chromosome (YAC) clones, because they span > 100 kbp, will provide attractive material for initiating searches for such genes. Twenty-two YAC clones, each of which maps to a region of potential relevance either to aspects of the Down syndrome phenotype or to one of the other chromosome 21-associated genetic diseases, have been analyzed in detail. Clones total approximately 6,000 kb and derive from all parts of the long arm. Rare restriction-site maps have been constructed for each clone and have been used to determine regional variations in clonability, methylation frequency, CpG island density, and CpG island frequency versus gene density. This information will be useful for the isolation and mapping of new genes to chromosome 21 and for walking in YAC libraries.

Chromosome Mapping↗
PubMed1990

Potential gene sequence isolation and regional mapping in human chromosome 21.

The transcription start sites of many genes are associated with CpG-rich DNA regions (CpG islands) containing clusters of rare cutting, methylation-sensitive restriction enzyme sites [Bird, 1986]. To detect gene sequences from human chromosome 21, we have screened cloned DNA fragments from a chromosome 21-specific cosmid library for the presence of such restriction sites. Several DNA fragments containing rare cutter sites, including Sac II, were isolated and five of them partially characterized. The average insert size of the fragments was 38.4 kb. By using a panel of somatic cell hybrids, one insert was assigned to the distal part of region 21q21, three fragments to the region 21q22.1, and one sequence to the segment 21q22.2-22.3. Restriction mapping showed clusters of rare cutter sites in at least three of the cloned fragments, suggesting the presence of CpG islands. These fragments are thus good candidates for carriers of coding sequences.

Animals↗
PubMed1990

Molecular study of parental origin of extra chromosome 21 in regular and de novo translocation trisomies.

The parental origin of the extra chromosome 21 (or extra 21q) was determined in seven informative families with a Down syndrome (DS) child by using molecular polymorphisms. Five DS patients had regular trisomy, one a de novo 14/21 translocation and another a de novo 21/21 translocation or isochromosome 21q. In four families with regular trisomy, the extra chromosome was of maternal origin, and in one family it was paternally derived. In the two families with a de novo aberration, both the 14/21 translocation and 21/21 rearrangement originated during maternal meiosis. For a better evaluation of the stage of meiotic error and the occurrence of crossovers between nondisjoined chromosomes, the regional map position of four of the nine informative DNA markers, used in this study, was refined, leading to useful localizations in both centromeric and distal regions. Recombination events were found in two families with regular trisomy, one occurring between chromosomes 21 that failed to disjoin at maternal meiosis I, the other prior to a paternal meiosis II nondisjunction.

Blotting, Southern↗
PubMed1990

Pericentric inversion of chromosome 9: prevalence in 300 Down syndrome families and molecular studies of nondisjunction.

The incidence of Down syndrome (DS) families where one of the parents is an heterozygous carrier of pericentric inversion of the heterochromatic region of chromosome 9-inv(9) (qh) - was determined in 3 independent groups of 100 families each. The total number of 17 such families found in the sample is significantly greater than the expected number of 5.73 for a sample of non-DS families of equal size. Consequently, the statistical association of the presence of inv (9) (qh) in one parent with the birth of a DS offspring, and the correlative 3-fold increased risk of a DS child for such families, seem to be demonstrated. A study of the origin of nondisjunction, using restriction fragment length polymorphism (RFLP) segregation analysis with a sufficient number of chromosome 21 specific probes, has provided complete information in 7 of 8 available families. Although the statistical interpretation of the results is not straightforward, due to the small size of the sample, the observed data do not contradict the assumption that the presence of inv (9) (qh) in a parent increases, by a factor of about 3, the chance that the offspring will inherit an extra chromosome 21 from that parent. Nevertheless, gathering further data appears desirable because stronger evidence would have relevance both for clinical implications and for the understanding of the function of heterochromatin, particularly with respect to meiotic and mitotic processes.

Chromosome Inversion↗